Parasitic protozoa are responsible for a wide variety of infections in both humans and animals. Protozoans of the genus Eimeria cause coccidiosis, a widespread disease of domesticated animals that causes severe pathology in the intestines and ceca. The most pathological species in this genus include E. tenella, E. acervulina, E. mitis, E. necatrix, E. brunetti and E. maxima. Animal coccidiosis is generally spread by animals picking up the infectious organism from droppings on contaminated litter or the ground, or from food or drinking water. Coccidiosis is manifested by hemorrhage, accumulation of blood in the ceca, passage of blood in the droppings, weakness and digestive disturbances. The disease often terminates in the death of the animal, while those that survive severe coccidiosis infection have had their market value substantially reduced as a result of such infections. Coccidiosis is, therefore, a disease of great economic importance. Accordingly, extensive work has been done to find new and improved methods for controlling and treating coccidial infections in animals.
In the poultry industry, it is common practice to include anticoccidial agents in poultry feed for most of the bird's life to control or prevent coccidiosis outbreak. However, there is a risk that the causative organisms will develop resistance after continuous or repeated exposure to any particular anticoccidial agent. Furthermore, conventionally used anticoccidial agents such as sulfanilamides, nitrofurans, quinolines, antithiamines, benzoamides, and polyether-based antibiotics are often toxic to the hosts. Therefore, there is a continuing need to identify new anticoccidial compounds, preferably in a different chemical class from agents currently in use.
Parasitic protozoa are also responsible for a variety of human diseases, many of which are life threatening. Malaria remains a significant health threat to humans despite massive international attempts to eradicate the disease. Another parasitic disease, trypanosomiasis, poses health risks to millions of people across multiple countries in Africa, South and Central America, and Mexico. Visitors to these regions, such as business travelers and tourists, are also at risk for contracting parasitic diseases. There are two types of African trypanosomiasis, also known as sleeping sickness. One type is caused by the parasite Trypanosoma brucei gambiense, and the other is caused by the parasite Trypanosoma brucei rhodesiense. If left untreated, African sleeping sickness results in death. Chagas disease, caused by Trypanosoma cruzi, affects millions of people in South and Central America, and Mexico. Untreated Chagas disease causes decreased life expectancy and can also result in death. There is currently no drug available for the prevention of these diseases. Currently available treatments are not entirely effective, and can even be toxic to the patient. A need thus exists for an antiparasitic compound for humans that is more effective and less toxic than those currently available.
The risk of parasitic diseases is also present outside developing countries. Opportunistic infections in immunocompromised hosts caused by Pneumocystis carinii, Toxoplasma gondii, and Cryptosporidium sp. are becoming increasingly prevalent in developed countries. For example, toxoplasmosis, which is caused by the parasite Toxoplasma gondii, is found in countries throughout the world, including the United States. Pregnant women and those with weak immune systems are particularly susceptible to health risks resulting from Toxoplasma infection. Severe toxoplasmosis can result in damage to the brain, eyes, and other organs. Currently available treatments for toxoplasmosis, which are the drugs trisulfa-pyrimdine, sulfadiazine and pyrimethamine, are not effective, and can be toxic to the host. Therefore, there is a need for therapeutic agents to treat toxoplasmosis that are more effective and less toxic than currently available treatment agents.
PCT Published Application WO03/000682 discloses compounds of the formula:

PCT Published Application WO03/000689 discloses compounds of the formula:
